1019 Am. J. Trop. Med. Hyg., 60(6), 1999, pp. 1019–1023 Copyright  1999 by The American Society of Tropical Medicine and Hygiene RISK FACTORS FOR GAMETOCYTE CARRIAGE IN UNCOMPLICATED FALCIPARUM MALARIA RIC PRICE, FRANC ¸ OIS NOSTEN, JULIE A. SIMPSON, CHRISTINE LUXEMBURGER, LUCY PHAIPUN, FEIKO TER KUILE, MICHELE VAN VUGT, TAN CHONGSUPHAJAISIDDHI, AND NICHOLAS J. WHITE Shoklo Malaria Research Unit, Mae Sod, Tak Province, Thailand; Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand; Division of Infectious Diseases, Tropical Medicine and AIDS, Academic Medical Centers, University of Amsterdam, Amsterdam, The Netherlands; Centre for Tropical Medicine Nuffield Department of Clinical Medicine, John Radcliffe Hospital, Headington, Oxford, United Kingdom Abstract. The factors affecting the development of patent Plasmodium falciparum gametocytemia were assessed in 5,682 patients entered prospectively into a series of antimalarial drug trials conducted in an area of low and seasonal transmission on the western border of Thailand. Of the 4,565 patients with admission thick smear assess- ments, 110 (2.4%) had gametocytemia. During the follow-up period 170 (3%) of all patients developed patent ga- metocytemia, which in 89% had developed by day 14 following treatment. In a multiple logistic regression model five factors were found to be independent risk factors at presentation for the development or persistence of gameto- cytemia during follow up; patent gametocytemia on admission (adjusted odds ratio [AOR] = 7.8, 95% confidence interval [CI] = 3.7–16, P  0.001), anemia (hematocrit 30%) (AOR = 3.9, 95% CI = 2.3–6.5, P  0.001), no coincident P. vivax malaria (AOR = 3.5, 95% CI = 1.04–11.5, P  0.04), presentation with a recrudescent infection (AOR = 2.3, 95% CI = 1.3–4.1, P  0.004), and a history of illness longer than two days (AOR = 3.3, 95% CI = 1.7–6.6, P  0.001). Patients whose infections responded slowly to treatment or recrudesced subsequently were also more likely to carry gametocytes than those who responded rapidly or were cured (relative risks = 1.9, 95% CI = 1.3–2.7 and 2.8, 95% CI = 2.0–4.0, respectively; P  0.001). These data provide further evidence of important epidemiologic interactions between P. falciparum and P. vivax, and drug resistance and transmission potential. The life cycle of Plasmodium falciparum is dependent upon the production of viable sexual stages of the parasite and their appearance in sufficient numbers in the peripheral blood of the human host. These gametocytes can then be transmitted to a feeding anopheline mosquito and on to a new human host, thus completing the life cycle of the ma- laria parasite. In contrast to the treatment of the three other species of human malaria, most of the antimalarial drugs used to treat the asexual stages of P. falciparum malaria have little or no effects on the viability of mature gametocytes. The rate of production of gametocytes is influenced consid- erably by host factors, notably immunity, 1 and this may have significant epidemiologic consequences. Integrated malaria control programs that aim to reduce malaria transmission are often based on identifying those individuals most likely to transmit malaria. We investigated the factors that influence the production of gametocytes following uncomplicated fal- ciparum malaria in an area where there is a high prevalence of multidrug resistance, and a relatively low level of trans- mission and consequent background immunity. METHODS Study site. The study took place between 1990 and 1995 in patients living in a camp for displaced person of the Karen ethnic minority situated in an area of malarious hill forest on the western border of Thailand. During the five-year pe- riod, a series of 18 antimalarial drug studies were conducted to determine the optimum treatment of falciparum malaria in the face of a continuing decrease in mefloquine sensitivity. The epidemiology of malaria at this site has recently been described in detail. 2 Transmission of malaria is low (each person experiencing approximately one vivax and one fal- ciparum malaria infection every two years) and seasonal in this area. Nearly all falciparum malaria infections are symp- tomatic, and the treatments of every episode have been doc- umented. Patients. Patients of all ages were recruited into these stud- ies provided that they or their accompanying relatives gave fully informed consent. Each of the studies was approved by the Ethics Committee of the Faculty of Tropical Medicine of Mahidol University. All patients had slide-confirmed falcipa- rum malaria. Pregnant women, children weighing  5 kg, and patients with signs of severity or concomitant disease requir- ing hospital admission were all excluded. On admission, a questionnaire was completed recording details of symptoms and their duration, and the history of previous antimalarial medication (since health structures in the camp are the only source of antimalarial drugs in this area, the history is gen- erally a reliable guide to pretreatment). A full clinical exam- ination was also completed and blood was taken for routine hematology and quantitative parasite counts. Drug treatment significantly affects the subsequent devel- opment of gametocytemia 3 at this study site, and for this reason patients in this study were categorized into four an- timalarial treatment groups for the purposes of this analysis: mefloquine (single or split dose without artemisinin deriva- tives), halofantrine (high or low dose), artemisinin deriva- tives (artesunate or artemether with and without mefloquine), and quinine (Table 1). Drug administration was observed in all cases. All patients were examined daily until they became asymptomatic and aparasitemic, and were then seen weekly during the follow-up period. Before 1993, this was for was four weeks, and since then for nine weeks. A blood smear was taken at each weekly visit or if symptoms returned be- tween follow-up appointments. Recrudescent infections were treated with a seven-day regimen of quinine sulfate (30 mg of salt/kg/day) in combination with tetracycline (16 mg/kg/ day) if more than eight years old, or more recently with a seven-day regimen of artesunate or artemether (12 mg/kg given over a seven-day period).